Borisenko served as a flight engineer onboard Soyuz TMA-21 for Expedition 27, the 27th long-duration mission to the International Space Station (ISS). He also served as the commander of the International Space Station for Expedition 28. He launched for the second time in October 2016 onboard Soyuz MS-02 as a flight engineer of Expedition 49 and Expedition 50. He returned to Earth in April 2017.
Borisenko is married to Natalia Aleksandrovna Borisenko. They have a son, Ivan and a daughter. His parents, Ivan Andreevich and Natalia Mikhailovna Borisenko, reside in St Petersburg. His hobbies include fishing, badminton, and road trips.
Borisenko graduated from the Leningrad Physics and Mathematics School #30 in 1981. He then entered the Leningrad Military Mechanical Institute and graduated in 1987 with the qualification "Flight and Control Dynamics".
Following graduation from the institute Borisenko worked for a military unit from 1987–1989. In 1989, he started working at RSC Energia where he was responsible for the Mir motion control system and took part in the Mission Control Center - Moscow (MCC-M)) onboard systems operation analysis board. In 1999, Borisenko was a shift flight director at the MCC-M, first for the Mir space station and then for the International Space Station (ISS).
Borisenko was selected as a cosmonaut candidate from RSC Energia on May 29, 2003. He started basic spaceflight training in June, 2003 and completed it in June, 2005 by passing the state exams with excellent grades. He received qualification of test-cosmonaut on July 5, 2005 from the Interdepartmental Qualification Commission. From July 2005 to August 2008 he participated in advanced space flight training. From August 2008 to March 2009 he trained as an Expedition 24/25 backup crewmember. Since March 2009 he trained with the Expedition 23/24 back up crew as a station commander and Soyuz TMA flight engineer.
Borisenko flew into space for the first time as a Flight Engineer for the ISS long duration Expedition 27/28 missions. The Soyuz TMA-21 spacecraft carrying Borisenko, cosmonaut Aleksandr Samokutyayev and NASA astronaut Ron Garan launched on schedule from the Baikonur Cosmodrome's Gagarin's Start launch pad, at 23:18:20 UTC on April 4, 2011. The launch of Soyuz TMA-21 was dedicated to the 50th anniversary of the first manned space flight by Yuri Gagarin performed in 1961.
After 2 days of autonomous flight, the Soyuz TMA-21 spacecraft docked with the International Space Station (ISS) on April 6 at 23:09 UTC.
At 11:41 a.m. EDT Sunday, May 22, 2011, Dmitri Kondratyev who had been the commander of Expedition 27, conducted a change of command ceremony with Andrey Borisenko. Andrey then commanded Expedition 27 and continued in command of Expedition 28 until he handed over the duties to Flight Engineer Mike Fossum on September 15, 2011.
Borisenko concluded his stay aboard the ISS, when his spaceship, Soyuz TMA-21 undocked from the Russian segment's Poisk module at 00:38 UTC on September 16,. On the same day, the Soyuz TMA-21 capsule carrying Borisenko and his two crew mates, Alexander Samokutyaev and Ron Garan touched down (3:59:39 UTC) at 93 miles southeast of the city of Zhezkazgan in Kazakhstan. During the Soyuz re-entry, repeated calls to the spacecraft from the Russian Mission Control in Korolyov, near Moscow, went unanswered for several minutes. Communication was eventually established between the crew and a plane circling the landing site.
On the ground, Borisenko appeared to be in good spirits as he flashed up an enthusiastic "thumbs-up" signal shortly after he was pulled out of the Soyuz landing capsule. He and his colleagues were carried on their chairs to a makeshift inflatable hospital for further medical check ups. After attending the traditional greeting ceremony at the airport in Karaganda, Kazakhstan, Borisenko boarded a plane to return to the training base in Star City, Russia.
Borisenko launched for the second time to the ISS onboard Soyuz MS-02 as flight engineer, alongside Soyuz commander Sergey Ryzhikov and NASA astronaut and Expedition 50 commander Shane Kimbrough. They returned safely to Earth on April 10, 2017 after 173 days on orbit.